Isolated complex I deficiency is the commonest mitochondrial respiratory chain defect observed in children with mitochondrial disease. It is associated with a range of clinical features, including fatal congenital lactic acidosis, cardiomyopathy, encephalopathy, dystonia, myopathy, hypopnoea, hepatopathy and optic atrophy. The genetic aetiology of complex I deficiency is heterogeneous, with approximately 30% of children having mutations in the mitochondrial genome, while nuclear DNA mutations, in structural subunit and assembly genes, are thought to account for the remainder. At least nine nuclear genes encoding structural elements have been described, though how often mutations in these genes cause mitochondrial disease remains unknown.

A child with cystathionine beta-synthase deficiency developed cerebral edema 4 to 6 weeks after starting betaine therapy. There was no evidence of intracranial thrombosis, but there was widespread edema of the white matter. He recovered fully after emergency decompressive craniotomy and withdrawal of betaine.